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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline conform GLP study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study on skin sensitization already performed under Directive 67/548/EC, before REACH entered into force.
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River France (Cleon, France)
- Age at study initiation: 6 weeks
- Weight at study initiation: 250 - 550 g
- Housing: in groups according to EEC/86/609 in stainless stell mesh cages
- Diet (e.g. ad libitum): pelleted complete guinea pig diet, ad libitum
- Water (e.g. ad libitum): softened and filtered mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19+/-3°C
- Humidity (%): >/= 45%
- Air changes (per hr): >/= 22
- Photoperiod (hrs dark / hrs light): 12/12

Route:
intradermal and epicutaneous
Vehicle:
other: absolute ethanol
Concentration / amount:
Induction:
- intradermal: 10% (w/w)
- topical: 60% (w/w)

Challenge:
- topical: 60% (w/w)
Route:
epicutaneous, occlusive
Vehicle:
other: absolute ethanol
Concentration / amount:
Induction:
- intradermal: 10% (w/w)
- topical: 60% (w/w)

Challenge:
- topical: 60% (w/w)
No. of animals per dose:
Number of animals in test group: 20
Number of animals in negative control group: 10
Details on study design:
Control: 5 males, 5 females
Treatment group: 10 males, 10 females


- Intradermal induction
Administration area: 2x4 cm on the clipped dorsal shoulder region
Time of injection: day 1
Three pairs of intradermal injections were performed to the retroscapsular region left and right of the spine, in an approx. 2x4 cm area

1. Freund's complete adjuvant at 50% (v/v) in an isotonic injectable aolution
2. test article in a 10% (w/w) solution in absolute ethanol
3. mixture 50/50 (v/v): test article in a 20% (w/w) suspensin in absolute ehtanol + Freuns's complete adjuvant at 50% (v/v) in an isotonic injectable solution, i.e. a final 10% concentration of the test item.
Injection of the test item in a 10% solution provoked a moderate irritation with burnt appearance to the injection sites during the preliminary study.

- Topical application (48 h exposure)
Application area: clipped and shaved area, corresponding to that used for intradermal injections
Time of administration: day 9
0.5 mL test item in a 60% (w/w) paste in absolute ethanol
The test item was applied under an occlusive dressing composed of filter paper 2x4 cm maintained in contact with the skin with a waterproof and hypo-allergenic tape.Fixing of this tape was reinforced with a 4 cm wide linen adhesive tape applied on a hydrophilic gauze pad covering the whole clipped surface to avoid possible irritation by the adhesive tape.
As this application only provoked a weak irritation during the preliminary study, a skin painting was performed during the main study on day 8, with 0.5 mL of sodium lauryl sulphate at 10% (w/w) in Codex paraffin to create irritation.

- Control group
The intradermal injections and the topical occlusive application for 48 h were carried out under the same conditions as in the treated group, absolute ethanol replacing the test item.

- Rest period: day 11 to 22
Challenge controls:
- Challenge application
day 22
Application area: a 2x2 cm area on the left flank of each animal, close-clipped and shaved
The topical occlusive application for 24 h was performed in the treated group and the control group with the test item in a 60% (w/w) paste in absolute ethanol and at the dose level of 0.5 mL. The vehicle was also applied during challenge.
The cutaneous macroscoppic examinations were performed 24 and 48 h after removel of the occlusive dressing to the challenge applications sites, according to the Magnusson & Kligman scale.
Histopathological examination of the skin was performed for one animal of the treated group which showed doubtful macroscopic reaction at 24 h.
Positive control substance(s):
yes
Remarks:
DCNB (1-Chlor-2,4-Dinitrobenzol)
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
60 %
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 60 %. No with. + reactions: 1.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
60 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 60 %. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
60 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 60 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
60 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 60 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
From the results obtained under the experimental conditions employed the test item is regared as not sensitising.
Executive summary:

Testing for sensitising properties of N,N’-Bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide was performed in male and female guinea pigs according to the Magnusson & Kligman test (PPMT). Intradermal induction was performed using 10 % N,N’-Bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide, topical induction with 60% substance in paste. The challenge was carried out with 60% N,N’-Bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide (epidermal) 12 days after the last induction application.

The test item induced allergic reactions in only one out of twenty animals.

N,N’-Bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide is regarded as not sensitising.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:
Migrated from Short description of key information:
N,N'-Bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide has been tested in one skin sensitization studies (Guinea pig maximization according to the Magnusson & Kligman to assess the sensitising potential of the test item. The test substance induced a weak allergic reaction in only 1/20 animals. According to the standard evaluation, this number is not high enough to be significant.

Justification for selection of skin sensitisation endpoint:
Guideline conform GLP study

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

There are no respiratory sensitization properties of the substance known in literature. Beyond this there is no hint of any sensitization property of the compound from the conducted skin sensitization study. Therefore, it is concluded that the subsance is not a respiratory sensitizer.


Migrated from Short description of key information:
Based on the existing data it is concluded that the substance is not a respiratory sensitizer.

Justification for classification or non-classification

A classification concerning respiratory sensitizing properties is not warranted as the classification criteria according to EU regulation 1272/2008 and 67/548 are not met.

The sensitization potential of N,N'-Bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide was investigated according to OECD Guideline 406. The test item topical challenge concentration chosen for the Guinea pig maximization according to the Magnusson & Kligman test was 60 %.
No deaths occurred during the study period. Only one of the treated animals showed a slight skin reaction.
The test substance did not show skin sensitizing properties according to the current OECD guidelines. Allergic skin reactions or case reports of acute contact dermatitis to N,N'
Bis(2,2,6,6-tetramethyl-4-piperidinyl)isophthalamide have not been described in the literature. Therefore, the substance does not have to be classified as a skin sensitizer.